# Experience-dependent maturation of prefrontal circuitry in control of social behavior

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $496,740

## Abstract

Social experience during childhood is essential to establish proper function in the adult prefrontal cortex (PFC)
and related behaviors including social behavior, a fundamental process across species. However, the specific
circuits that undergo social experience-dependent maturation to regulate social behavior are poorly
understood. Given that social process deficit is a common dimension of many neurodevelopmental and
psychiatric disorders, identifying the specific circuits sensitive to experience-dependent modulation will point
toward therapeutic targets that allow amelioration of social processing deficits shared across of range of
disorders. The objective of this study is to elucidate the PFC circuit mechanisms underlying social experience-
dependent maturation crucial to mediate proper social behavior. In mice, juvenile social isolation leads to adult
social behavior deficits and accompanies deficits in sub-cortically projecting deep layer medial PFC (mPFC)
pyramidal neurons. Among various sub-cortical targets, our preliminary study identified the limbic thalamus
which receives and relays signals to various components of the classical reward circuitry, as the most
prominent projection target from mPFC that is preferentially recruited by social interaction. Importantly, juvenile
social isolation reduced excitability of this projection neuron and increased their inhibitory drive. Among various
types of inhibitory neurons, a selective subclass of deep layer inhibitory neuron, known to be essential to
oscillate subcortically projecting deep layer cortical neurons, were the only population that exhibited elevated
excitability after juvenile social isolation. This project will test the hypothesis that juvenile social experience-
dependent maturation of deep layer mPFC projection neurons to limbic thalamus and its modulation by deep
layer mPFC inhibitory neurons drives coordinated activity in mPFC and limbic thalamus to effectively modulate
social behavior. We will test this hypothesis by integrating techniques to measure (fiber photometry imaging,
patch-clamp/ in vivo electrophysiology) and manipulate (optogenetics/chemogenetics) the activities of selective
circuits during social behavior in mice.

## Key facts

- **NIH application ID:** 10401748
- **Project number:** 5R01MH118297-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Hirofumi Morishita
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $496,740
- **Award type:** 5
- **Project period:** 2019-07-18 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401748

## Citation

> US National Institutes of Health, RePORTER application 10401748, Experience-dependent maturation of prefrontal circuitry in control of social behavior (5R01MH118297-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10401748. Licensed CC0.

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